Editors: Gérard Chaouat, Olivier Sandra, & Nathalie Lédée

Immunology of Pregnancy 2013

eBook: US $149 Special Offer (PDF + Printed Copy): US $268
Printed Copy: US $194
Library License: US $596
ISBN: 978-1-60805-734-4 (Print)
ISBN: 978-1-60805-733-7 (Online)
Year of Publication: 2013
DOI: 10.2174/97816080573371130101

Introduction

Since a September, 1992, Nature article which read: “Can there be life without LIF?”, researchers now realize that the maternal immune system is both a foe (it can reject the conception) and a friend (immune cells and molecules are also necessary for successful pregnancy). Leukemia Inhibitory Factor (LIF) when absent, prevents embryo implantation in rodents. From fecundation to parturition, immunity acts as a Janus, required but potentially dangerous. However, the complexity and the diversity of immunity in pregnancy deters many from entering the field. This book will try to give a complete overview of immunity from gametes till parturition, in brief, but with complete chapters and subsections, each written by specialists in the field.

The importance of the topic relies not only on “the riddle of the fetal allograft”, which is per se fascinating, but on its consequences, linked to the development of IVF and in general, Assisted Reproductive Technologies (ART) / Medicine. Since the discovery that there would not be (mammalian) life without LIF, it has become clear that Immune Molecules, and in general, transient post mating inflammatory reactions are required for successful implantation. Disruptions of this process can lead to implantation failure / sterility.

In later stages of pregnancy immunological cells, mostly of the innate immune system, control formation of local spiral arteries. Finally, a state of tolerance establishes itself, whose “break’ leads to immune abortion and the vascular bed is further transformed and enlarged, till delivery, and here again “immunological cytokines” do play a major role and can eventually cause immune mediated abortion.

Failure of, not just, the cytokine and cell recognition mediated dialogue, but also the pre and peri-implantation “preparation of the uterus”, as stated, leads to sterility, early pregnancy loss and recurrent abortions. There is also an increasingly stronger argument to implicate immunology in pre-eclampsia. Further still, immunology is also implicated in the control of local infection, mother to child transmission of pathogens (notably, but not limited to, HIV). Finally, pregnancy is the only known physiological phenomenon where the once named “suppressor T cells,” re-emerge as “regulatory T cells”, and play a cardinal role.

This E-book provides a complete compendium of gynecological immunology, spanning from fecundation to delivery. Topics also include the role of various cell types (such as T regs ad NK cells) in implantation and uterine changes as well as the genetic regulation of immunological processes. As such it will be of interest not only to fundamental and reproductive immunologists, but more importantly, clinicians in obstetrics and gynecology.

Indexed in: Book Citation Index, Science Edition, EBSCO.

Preface

Reproductive Immunology is (too) often seen as dealing only with the paradox of the survival in a theoretically hostile maternal immune environment of the “foetal allograft “in mammals.

Thus, most authors date its start from 1953 Medawar’s now citation classic.

However, as will be discussed in this eBook, the “danger” theory enunciated by Polly Matzinger states that there is no problem in such an intimate but peculiar, since necessary, tissular relationship. That immunity might threaten Reproduction is for her an evolutionary nonsense. In fact, Matzinger’s interest in Immunology was at least partly triggered by discussions she had about the “paradox” of placental pregnancy long before she even thought she will one day run the famous “ghost lab” at NIH.

We will, of course, indeed discuss her theory in one chapter of this eBook.

But anyway, it is an error to believe the topic is limited to the relationship between the mother and the foetus: the field is dealing with gametes, since they are necessary to Reproduction, and since pregnancy starts with Fecundation. In fact, so did Reproductive Immunology when it started in 1899 as, independently, Landsteiner and Metchnikoff obtained hetero antibodies against sperm. One year afterwards, Metalnikoff obtained the 1st (immobilizing) iso antibodies to spermatozoa by injecting guinea pigs with their own sperm.

This, incidentally, and it is too often forgotten by mainstream Immunologists, was one of the first demonstrations of “horror autotoxicus”, as Erlich would later (re) name autoimmunity.

Much later, the first steps forwards in Reproductive Immunology were these of Voisin, Barber and Delaunay on one hand in 1951, Freund, Lipton, and Thompson in 1953.

These were followed by Medawar’s lecture, and the seminal experiments of Billingham, with Beer, and later on Head.

It is interesting and noteworthy to recall that when I joined, initially for what would become my Md. Thesis and my first real Scientific paper the INSERM U23 lab, under Guy Voisin’s direction, I was placed in the same room as Marta d’Almeida, Françoise Chadenier and Francine Toullet, who while working on anti sperm immunity taught me the initial steps in Immunology.

In Francine’s lab, the top techniques at the time were sperm cytotoxicity and sperm agglutination for assessment of humoral immunity, as well as DTH measurements by Evans blue rat skin permeation and DTH caliper measurements of footpad swelling.

Another part of the unit was testing whether or not T and B cells were morphologically distinguishable including by electron microscopy studies conducted by Philippe le Bouteiller and Simone Righenzi…

The discovery of T and B cells cooperation, Gershon’s description of Ts (now rejuvenated as T regs) hit the field, as well as NK cells, albeit I must admit that when Herbermann described initially Natural killing, a 5% max killing of Yac-1 target cells in a 51 Cr CRT was judged by many as an artefact. Of course, at that time the mains controversies were centring on the eventual existence of paternal MHC antigens at the interface, whereas it was also the age of the first lectures in Saint Antoine and Pasteur of GP Talwar about the future of contraceptive vaccines (anti hCG).

40 years afterwards, we are no longer dealing with “lymphocytes” and antibodies, but with a variety of cell populations, which we can isolate, thanks not to their morphology, but to a variety of cell surface or cytoplasm markers. Cell to cell communication is effected by a variety of well defined soluble molecules (while many of the “factors” which were described in the dawn of cellular immunology such as Ag-specific TsF, including “TsF1” and “TsF2”, genetically restricted macrophage helper factor, etc… have joined the infamous I-J region in oblivion).

When Tom Wegmann wrote –and it was a conceptual revolution- that the embryo is bathed in a sea of cytokines, he was referring to at best 10 of them, and Tim Mossman had just delineated Th1 from Th2 cells/cytokines.

Now we have more than 35 interleukins, several super families, toll receptors. We know that contraceptive vaccines are feasible (including, one forgets it often, in animal species, where one, for example, has helped to control fox mediated rabies propagation). In fact, Immunology is too often neglected by many obstetricians, who seem to forget (ignore?) Nature’s Editorial “would there be life without LIF”, pinpointing by then that immune molecules can be necessary for pregnancy.

Another reassessment was the realization of the role of NK cells, “killers become builders”….

And so on….

Thus, the field is now established by its own. Parallel developments in ART have emphasized, I repeat, that Immunology could be as important as Endocrinology, whereas more and more facts are implying Immunology in such syndromes as pre eclampsia.

But it is a rapidly moving field, so, albeit the last (and excellent it is) treatise dates from only 2006, the need for another update emerged. The eBook format is excellent in that respect, allowing relatively rapid publication and possibly regular rapid updates.

Hence, this publication appears.

In keeping with the rapid evolution of the discipline, I preferred not to be preposterous, and thus to name it “Immunology of Pregnancy 2013” rather than another “Immunology of Pregnancy”.

Now, who should read this eBook?

Mainstream Immunologists, whose presence on this planet has been dependent on Immunological intervention, a fact they are for most of them surprisingly unaware: but they should also discover a very fascinating New World, and I recall the surprise of a major actor in the cytokine field, who actually discovered the first Interleukin (IL-1), after a lecture I gave at the FIMSA (Federation of meeting, in Hang Zhou, China “I never thought there were so many important cytokines in the uterus!”.

But this eBook is also aimed at Gyn/Obs clinicians…. I know that Immunology has its Jargon, but this is as inescapable as “strangeness” in Nuclear physics and cosmology. Without suggesting the clinicians to make a similar effort as the one required for a Beotian to enter quantum mechanics, we really believe that comprehension of Immune events of pregnancy is now a must for them, and will lead them to new diagnosis and therapeutic tools/ behaviour.

Finally, this eBook is of course aimed at the old and, more important the young Scientists in the field.

To them, we state that “we hope that this eBook is made for you”…

We have tried to encompass most of the important topics (with the exception of Allergy and the foetus and neonate, a topic which deserves a specialized treaty, per se, and stress, since Neuro Immunology is a field by itself, albeit we allude to it in several sections).

Finally, of course I thank here the numerous co-authors for their dedication to the task of writing a relatively concise but complete sub chapter or chapter

Megève, French Alps, August 1st 2011. Paris 1st May 2012.

Gérard Chaouat
Director of Research Emeritus
U976 INSERM/UMR 976 CNRS Hôpital Saint Louis 75010
Paris
France

P.S. Three Last Words:

  1. The views expressed in the chapters are my own, and do not commit any of the other contributors.
  2. The chapters in this eBook are made so that, albeit they complete each other, each one can be read independently. Thus, “redites” are unavoidable, and in fact necessary, as are left contradictive opinions when a matter remains controversial.
  3. The eBook planned originally a chapter on Immunity and Infection /parasites during pregnancy. Because of health problems and then death of the principal author for this chapter, this plan had to be abandoned (see last pages). But we hope, thanks to the eBook format, to be able to provide later on this chapter in electronic form.


RELATED BOOKS

.Personalized Immunotherapy for Tumor Diseases and Beyond.
.Frontiers in Clinical Drug Research – Anti Allergy Agents.
.Meta-inflammation and Obesity.
.Antibodies Applications and New Developments.